1. The beta2-adrenergic modulator celiprolol reduces insulin resistance in obese Zucker rats.
- Author
-
Jacob S, Fogt DL, Dietze GJ, and Henriksen EJ
- Subjects
- Adrenergic beta-Antagonists administration & dosage, Animals, Antihypertensive Agents administration & dosage, Antihypertensive Agents pharmacology, Biological Transport, Active drug effects, Blood Glucose metabolism, Celiprolol administration & dosage, Deoxyglucose metabolism, Female, Hypertension metabolism, Insulin blood, Metoprolol administration & dosage, Metoprolol pharmacology, Muscle, Skeletal drug effects, Muscle, Skeletal metabolism, Rats, Rats, Zucker, Adrenergic beta-Antagonists pharmacology, Celiprolol pharmacology, Insulin Resistance, Obesity drug therapy, Obesity metabolism
- Abstract
Essential hypertension is associated with an increased incidence of insulin resistance of skeletal muscle glucose transport. The present study determined if celiprolol, an antihypertensive agent with selective beta1-adrenoceptor antagonist and additional beta2-agonistic properties, administered by gavage either acutely (3 hr) or chronically (14 d), had a direct effect on improving glucose tolerance and insulin-stimulated glucose transport activity (using 2-deoxyglucose (2-DG) uptake) in isolated epitrochlearis muscles of the insulin-resistant obese Zucker rat. The effects of a selective beta1-blocker, metoprolol, were also assessed. Acute administration of celiprolol, but not metoprolol, increased insulin-stimulated 2-DG uptake in muscle by 22% (p<0.05). Chronic celiprolol treatment significantly lowered fasting plasma insulin (22%) and free fatty acids (40%) in comparison to obese control values. Moreover, chronic celiprolol administration decreased the glucose-insulin index (calculated as the product of the glucose and insulin areas under the curve during an oral glucose tolerance test), by 32% (p<0.05) compared to obese controls, indicating that peripheral insulin action was increased. Indeed, insulin-stimulated skeletal muscle 2-DG uptake was enhanced by 49% (p<0.05) in these celiprolol-treated obese animals. Metoprolol was without significant effect on any of these variables following chronic administration. These findings indicate that, in this animal model of insulin resistance, the beta1-antagonist/beta2-agonist celiprolol has a specific effect of improving insulin-stimulated skeletal muscle glucose transport that is independent of any hemodynamic alterations.
- Published
- 1999
- Full Text
- View/download PDF